Persistent infection of mink with Aleutian mink disease parvovirus (ADV) leads to progressive immune disorder characterized by high levels of antiviral antibodies, immune complex disease and infection of macriphages via an antibody dependent mechanism (ADE). Virus is neutralized in vitro, but not in vivo, and infectious immune complexes occur. Capsid based vaccines are uniformly ineffective and induce acclerated disease. Major goals are: to correlate specific genomic sequences to functional correlates, such as pathogenicity determinants and strain variation; to characterize an ADV-binding protein (ABP)on the surface of susceptible cells that specifically binds ADV capsids and is the putative cellular receptor: and to study the actual structure of the ADV virion. Understanding of the structure at high resolution will enable us to (a) map epitopes and pathogenicity determinants to discreet coordinates on the viral particle, (b) relate structural features to the unique biology of ADV in vivo. In the past year, work on this project led to a number of findings. By studying additional chimeric and site-directed mutant ADVs, we found that the expression of pathogenicity requires cooperative interactions of non-adjacent capsid protein amino acids, and confirmed that the non-structural proteins do not play a significant role in pathogenicity. Studies using antibodies against short capsid protein peptides indicate that a single epitope is involved with virus neutralization, immune complex formation, and ADE. This finding may explain the failure of capsid based vaccines.